LGMD2IPhase 1/2NCT02841267
A Trial of PF-06252616 in Ambulatory Participants With LGMD2I
A Phase 1/2 study testing PF 06252616 in people with LGMD2I, run by Kathryn Wagner at 1 site in United States.
Trial summary
The investigational product PF 06252616, a humanized anti myostatin monoclonal antibody that neutralizes myostatin (GDF8) is in development for the treatment of Limb Girdle Muscular Dystrophy 2I (LGMD2I) to preserve and/or improve muscle function. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- LGMD2I
- What is being tested?
- PF 06252616
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2016to Jan 2019
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female patients age ≥ 18
- Diagnosis of LGMD2I as defined by clinical presentation consistent with LGMD2I and FKRP gene testing showing biallelic alterations known or likely to be pathogenic. Diagnosis must be confirmed in subject's medical history and by genetic testing obtained during routine clinical care for diagnostic purposes as reported from an appropriate regulated laboratory using a clinically validated genetic test (genetic testing is not provided by the sponsor).
- Ability to walk/run 10m
- Ability to rise from chair
- Adequate hepatic and renal function on screening laboratory assessments
- Iron content estimate on the screening liver MRI within the normal range as determined by R2* value (R2* ≤ 139 Hz at 3.0T).
- Participant must provide written informed consent for participating in study.
- Participant must possess the ability, per the Principal Investigator (PI), to understand and comply with protocol instruction for the entire duration of the study.
Who cannot join
- Known cognitive impairment or behavioral issues that would impede the ability to provide informed consent or to follow study instructions.
- History of major surgical procedure within 6 weeks of signing the informed consent or planned surgery during the study.
- Any injury which may impact functional testing. Previous injuries must be fully healed prior to consent. Prior lower limb fractures must be fully healed and at least 3 months from injury dates.
- Previous treatment with another investigational product within 30 days or 5 half-lives, (whichever is longer) prior to consenting.
- Corticosteroid treatment within 3 months prior to consenting.
- Compromised cardiac function (left ventricular ejection fraction <50%).
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- Unwilling or unable (e.g. metal implants, requires sedation) to undergo examination with closed MRI without sedation.
- History of allergic or anaphylactic reaction to a therapeutic or diagnostic protein.
- Female subjects who are pregnant or nursing.
- Subjects who, are biologically capable of having children who are unwilling or unable to use highly effective methods of contraception (as outlined in this protocol) during sexual activity for the duration of the study and through completion of final study visit.
- Predisposition to iron accumulation. (Serum iron >1.2 X ULN, serum ferritin >1.2 ULNN).
- Underlying disposition for bleeding disorder on screening laboratory assessment (PT/INR>1.25 X ULN, aPTT > 1.25 ULN, fecal occult blood is positive)
- Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, neurologic, or allergic disease.
- Unwillingness or inability to comply with the requirements of this protocol (in the opinion of the PI) including, but not limited to, the presence of any condition (physical, mental, or social) that is likely to affect the participant's ability to return for study visits or adhere to the visit schedule.
Trial locations and contacts
1 site in 1 country.
United States1 site
Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
Baltimore, Maryland, 21205
About this study
Official title: A Phase 1b/2, Open-Label, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics and Pharmacodynamics of PF-06252616 in Ambulatory Participants With LGMD2I
The investigational product PF 06252616, a humanized anti myostatin monoclonal antibody that neutralizes myostatin (GDF8) is in development for the treatment of Limb Girdle Muscular Dystrophy 2I (LGMD2I) to preserve and/or improve muscle function.
This study will provide the clinical assessment of the safety, tolerability, Pharmacokinetics and Pharmacodynamics of PF 06252616 following repeat IV doses in ambulatory adults with LGMD2I.
Read the detailed description
This study is a Phase 1b/2, open-label multiple ascending dose escalation study to evaluate the safety, tolerability, efficacy, PK and PD of PF 06252616 in ambulatory adults with LGMD2I. The study design is intended to determine the optimal safe and pharmacologically active dose of PF 06252616 in LGMD2I while providing an opportunity for all subjects to receive active drug for a rare and disabling disorder. The study will be conducted in three periods: Lead-In, Treatment and Follow-up periods. The Lead-In and Follow-up periods will each be 16 weeks to allow an assessment of the change of various outcome measures of this period of time and comparison of change in function before, during and after treatment. The Treatment period will be 32 weeks. Three cohorts of participants will be enrolled and receive escalating doses of PF 06252616. The first cohort will have the option to crossover to the highest dose.
- Conditions
- LGMD2I
- Being tested
- PF 06252616
- Medical subject headings
- Muscular Dystrophy, Limb-Girdle, Type 2I
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PF 06252616Drug
| Study group | Role | What they receive |
|---|---|---|
| Low Dose, Cohort 1 | Active comparator | 4 subjects will be enrolled in cohort 1 and will receive an initial dose of 5mg/kg PF 06252616 IV every 4 weeks. Following 32 weeks of treatment and a safety review, if no stopping rules have been met, subjects will be receive an additional 32 weeks of treatment with 40 mg/kg PF 06252616 IV every 4 weeks. Receives: Drug: PF 06252616 |
| Middle dose, Cohort 2 | Active comparator | 8 subjects will be enrolled in cohort 2 and receive 20 mg/kg of PF 06252616 IV every 4 weeks for 32 weeks. Receives: Drug: PF 06252616 |
| High dose, Cohort 3 | Active comparator | 8 subjects will be enrolled in cohort 3 and receive 40 mg/kg of PF06252616 IV every 4 weeks for 32 weeks. Receives: Drug: PF 06252616 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Dose Limiting or Intolerability Treatment Related Adverse Events
Adverse events include subject-reported symptoms as well as clinically-significant changes in laboratory testing, vital signs, and suicide screening (based on the Columbia Suicide Severity Rating Scale).
Measured: Baseline through 64 weeks
Secondary outcomes (10)
Maximum Observed Serum Concentration at Steady State (Cmax, ss) of GDF-8
The concentration of myostatin (GDF-8) was measured in serum 2 hours after dose administration at two visits (Day 337 and Day 393 for Cohort 1; Day 113 and 169 for Cohorts 2 and 3)where drug concentration had reached steady state. The highest concentration from these two time points was averaged for each cohort.
Measured: Day 337 and Day 393 for Cohort 1; Day 113 and 169 for Cohorts 2 and 3
Minimum Observed Serum Trough Concentration at Steady State (Ctrough,ss) of GDF-8
The concentration of myostatin (GDF-8) was measured in serum prior to dose administration at two time points (Day 337 and Day 393 for Cohort 1; Day 113 and 169 for Cohorts 2 and 3) where drug concentration had reached steady state. The lowest concentration from these two time points was averaged for each cohort.
Measured: Day 337 and Day 393 for Cohort 1; Day 113 and 169 for Cohorts 2 and 3
Maximum Observed Serum Concentration (Cmax) of PF-06252616
The peak concentration of study drug (PF-06252616) was measured in serum following dose administration at two time points (Day 113 and Day 169) where drug concentration had reached steady state. The higher concentration from these two time points was averaged for each cohort.
Measured: Day 113 and Day 169
Minimum Observed Serum Trough Concentration (Ctrough) of PF-06252616
The peak concentration of study drug (PF-06252616) was measured in serum prior to dose administration at two time points (Day 113 and Day 169) where drug concentration had reached steady state. The lower concentration from these two time points was averaged for each cohort.
Measured: Day 113 and Day 169
Immunogenicity: Incidence of Anti-drug Antibody
Blood samples were tested for the presence of anti-drug antibodies prior to the initiation of study drug, at dose escalation (Cohort 1 only), and at 3 separate time points after the last dose was given.
Measured: Baseline through 96 weeks
Mean Change From Baseline in 10 Meter Walk/Run Time in Seconds
Subjects are asked to run or walk as quickly as possible for 10 meters from a standing position. The total time to traverse 10 meters is recorded in seconds.
Measured: Baseline through 32 weeks
Mean Change From Baseline of Forced Vital Capacity in Liters
The total forced vital capacity was measured using a bedside spirometer. The best of 3 trials was recorded.
Measured: Baseline through 32 weeks
Mean Change From Baseline in 2MWD in Meters
Average change in distance (in meters) walked in 2 minutes.
Measured: Baseline through 32 weeks
Mean Change From Baseline in TUG in Seconds
The timed-up-and-go test (TUG) is the total time it takes the subject to rise from a seated position, walk to a marker 3 meters away, return to the chair, and sit.
Measured: Baseline through 32 weeks
Mean Change From Baseline in Muscle Strength as Measured by Modified MRC Scale
Twenty-two muscle groups were measured on a modified MRC scale ranging from 1 through 12. The total scores from all 22 muscle groups were added to generate a summary score ranging from 12 to 264 with higher scores signifying greater strength. The change in summary score was calculated over the first 32 weeks of treatment.
Measured: Baseline through 32 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2016 (estimated)
- Study startJul 2016
- Primary completionJan 2019
- Study completionJan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for LGMD2IStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kathryn Wagner
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Responsible party
- Sponsor-investigator, Kathryn Wagner, Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
- Investigators
- Kathryn R Wagner, MD/PhD, Principal investigator, Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02841267
- Sponsor's protocol ID
- WI203720
- Status last verified
- Sep 2020
- First submitted
- 12 Jul 2016
- Last updated
- 19 Oct 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Leung DG, Bocchieri AE, Ahlawat S, Jacobs MA, Parekh VS, Braverman V, Summerton K, Mansour J, Bibat G, Morris C, Marraffino S, Wagner KR. Longitudinal functional and imaging outcome measures in FKRP limb-girdle muscular dystrophy. BMC Neurol. 2020 May 19;20(1):196. doi: 10.1186/s12883-020-01774-5.
PubMed 32429923
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b/2, Open-Label, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics and Pharmacodynamics of PF-06252616 in Ambulatory Participants With LGMD2I
- ClinicalTrials.gov ID
- NCT02841267
- Acronym / sponsor ID
- WI203720
- Conditions
- LGMD2I
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Kathryn WagnerUniversity, hospital or other
- Collaborators
- Pfizer
- Study start
- Jul 2016
- Primary completion
- Jan 2019 (actual)
- Study completion
- Jan 2019 (actual)
- First posted
- 22 Jul 2016 (estimated)
- Results
- Posted 19 Oct 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigational product PF 06252616, a humanized anti myostatin monoclonal antibody that neutralizes myostatin (GDF8) is in development for the treatment of Limb Girdle Muscular Dystrophy 2I (LGMD2I) to preserve and/or improve muscle function.
This study will provide the clinical assessment of the safety, tolerability, Pharmacokinetics and Pharmacodynamics of PF 06252616 following repeat IV doses in ambulatory adults with LGMD2I.
Detailed description
This study is a Phase 1b/2, open-label multiple ascending dose escalation study to evaluate the safety, tolerability, efficacy, PK and PD of PF 06252616 in ambulatory adults with LGMD2I. The study design is intended to determine the optimal safe and pharmacologically active dose of PF 06252616 in LGMD2I while providing an opportunity for all subjects to receive active drug for a rare and disabling disorder. The study will be conducted in three periods: Lead-In, Treatment and Follow-up periods. The Lead-In and Follow-up periods will each be 16 weeks to allow an assessment of the change of various outcome measures of this period of time and comparison of change in function before, during and after treatment. The Treatment period will be 32 weeks. Three cohorts of participants will be enrolled and receive escalating doses of PF 06252616. The first cohort will have the option to crossover to the highest dose.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Low Dose, Cohort 1 | Active comparator | Drug: PF 062526164 subjects will be enrolled in cohort 1 and will receive an initial dose of 5mg/kg PF 06252616 IV every 4 weeks. Following 32 weeks of treatment and a safety review, if no stopping rules have been met, subjects will be receive an additional 32 weeks of treatment with 40 mg/kg PF 06252616 IV every 4 weeks. |
| Middle dose, Cohort 2 | Active comparator | Drug: PF 062526168 subjects will be enrolled in cohort 2 and receive 20 mg/kg of PF 06252616 IV every 4 weeks for 32 weeks. |
| High dose, Cohort 3 | Active comparator | Drug: PF 062526168 subjects will be enrolled in cohort 3 and receive 40 mg/kg of PF06252616 IV every 4 weeks for 32 weeks. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male and female patients age ≥ 18
- Diagnosis of LGMD2I as defined by clinical presentation consistent with LGMD2I and FKRP gene testing showing biallelic alterations known or likely to be pathogenic. Diagnosis must be confirmed in subject's medical history and by genetic testing obtained during routine clinical care for diagnostic purposes as reported from an appropriate regulated laboratory using a clinically validated genetic test (genetic testing is not provided by the sponsor).
- Ability to walk/run 10m
- Ability to rise from chair
- Adequate hepatic and renal function on screening laboratory assessments
Key exclusion criteria (14 listed)
- Known cognitive impairment or behavioral issues that would impede the ability to provide informed consent or to follow study instructions.
- History of major surgical procedure within 6 weeks of signing the informed consent or planned surgery during the study.
- Any injury which may impact functional testing. Previous injuries must be fully healed prior to consent. Prior lower limb fractures must be fully healed and at least 3 months from injury dates.
- Previous treatment with another investigational product within 30 days or 5 half-lives, (whichever is longer) prior to consenting.
- Corticosteroid treatment within 3 months prior to consenting.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PF 06252616 | Drug | High dose, Cohort 3, Low Dose, Cohort 1, Middle dose, Cohort 2 |
Primary outcome
Incidence of Dose Limiting or Intolerability Treatment Related Adverse Events
Time frame: Baseline through 64 weeks
Adverse events include subject-reported symptoms as well as clinically-significant changes in laboratory testing, vital signs, and suicide screening (based on the Columbia Suicide Severity Rating Scale).
10 secondary outcomes
Maximum Observed Serum Concentration at Steady State (Cmax, ss) of GDF-8
Time frame: Day 337 and Day 393 for Cohort 1; Day 113 and 169 for Cohorts 2 and 3
Minimum Observed Serum Trough Concentration at Steady State (Ctrough,ss) of GDF-8
Time frame: Day 337 and Day 393 for Cohort 1; Day 113 and 169 for Cohorts 2 and 3
Maximum Observed Serum Concentration (Cmax) of PF-06252616
Time frame: Day 113 and Day 169
Minimum Observed Serum Trough Concentration (Ctrough) of PF-06252616
Time frame: Day 113 and Day 169
Immunogenicity: Incidence of Anti-drug Antibody
Time frame: Baseline through 96 weeks
Mean Change From Baseline in 10 Meter Walk/Run Time in Seconds
Time frame: Baseline through 32 weeks
Mean Change From Baseline of Forced Vital Capacity in Liters
Time frame: Baseline through 32 weeks
Mean Change From Baseline in 2MWD in Meters
Time frame: Baseline through 32 weeks
Mean Change From Baseline in TUG in Seconds
Time frame: Baseline through 32 weeks
Mean Change From Baseline in Muscle Strength as Measured by Modified MRC Scale
Time frame: Baseline through 32 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32429923Leung DG, Bocchieri AE, Ahlawat S, Jacobs MA, Parekh VS, Braverman V, Summerton K, Mansour J, Bibat G, Morris C, Marraffino S, Wagner KR. Longitudinal functional and imaging outcome measures in FKRP limb-girdle muscular dystrophy. BMC Neurol. 2020 May 19;20(1):196. doi: 10.1186/s12883-020-01774-5.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kathryn R Wagner, MD/PhD principal investigator
Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing PF 06252616 in people with LGMD2I, run by Kathryn Wagner at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Oct 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Dose Limiting or Intolerability Treatment Related Adverse Events (time frame: Baseline through 64 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02841267, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2020.